phenobarbital

Phenobarbital is an anticonvulsant medication used to treat generalized and partial seizures and to induce sedation and anesthesia. Phenobarbital belongs to a class of medications known as barbiturates, and is a long acting medication. Phenobarbital induces sedation and reduces seizure activity by depressing the central nervous system and by enhancing the activity of gamma aminobutyric acid (GABA) the natural inhibitory chemical (neurotransmitter) in the brain.

Phenobarbital interacts with GABA-A receptors on nerve cells (neurons) and increases the influx of chloride ions, which results in enhanced GABA neurotransmission. GABA reduces the excitability of the neurons and reduces electrical activity and nerve signals that propagate seizure activity. In higher doses, phenobarbital induces sedation and anesthesia. Phenobarbital also enhances bilirubin metabolism and is used off-label to reduce bilirubin levels in newborns.

Phenobarbital is the oldest antiepileptic drug (AED) still in use, however it is not an FDA-approved drug because it was already in use before drugs needed FDA approvals. Uses of phenobarbital include the following:

Adult and pediatric patients:

• Status epilepticus, a state of prolonged seizure lasting for longer than five minutes
• Seizure disorders including partial, tonic-clonic and myoclonic seizures
• Sedative/hypnotic, including for preoperative sedation

Adult:

• Short-term treatment of insomnia

Pediatric:

• Hyperbilirubinemia, a condition with high bilirubin level, in newborn (off-label)

Orphan designations include:

• Neonatal seizures
• Brain damage caused by interrupted oxygen supply in newborn babies (neonatal hypoxic ischemic encephalopathy)

• Do not use phenobarbital in the following conditions:
  • Hypersensitivity to phenobarbital or any of its components
  • Porphyria, a group of disorders that affect the production of heme, a part of hemoglobin and other proteins
  • Severe liver function impairment
  • Kidney inflammation
  • Shortness of breath (dyspnea) or obstruction of airway
  • History of sedative hypnotic addiction
• Do not administer phenobarbital into an artery (intra-arterial) or in the tissue under the skin (subcutaneous)
• Commercial injection is highly alkaline and may cause tissue death (necrosis) if it leaks out of the vein (extravasation); exercise caution and treat with application of moist heat and injection of 0.5% procaine, if extravasation occurs
• May render oral contraceptives ineffective
• May cause paradoxical responses, especially in pediatric patients and patients experiencing acute or chronic pain
• May mask important symptoms when used in patients with acute or chronic pain; use with caution
• Use with caution in patients with fever, and debilitated patients
• Phenobarbital has been associated with cognitive deficits in children treated for complicated febrile seizures
• May cause respiratory depression, especially with intravenous administration; use with caution in respiratory disease and severe asthma (status asthmaticus)
• May cause central nervous system (CNS) depression and impair physical and mental abilities
• Concurrent use of phenobarbital with other CNS depressants including alcohol, narcotics, tranquilizers and antihistamines may result in additive CNS-depressant effects
• Use with caution in patients with severe anemia, patients experiencing depression, cardiac disease, hyperthyroidism, renal impairment, hypoadrenalism, hemodynamically unstable patients, and in patients with diabetes
• Do not discontinue abruptly; may increase seizure frequency; withdraw therapy gradually

Common side effects of phenobarbital include:

• Central nervous system depression
• Drowsiness
• Dizziness
• Vertigo
• Balance, coordination and speech impairment (ataxia)
• Slurred speech (dysarthria)
• Repetitive involuntary eye movements (nystagmus)
• Abnormal skin sensations (paresthesia)
• Irritability
• Restlessness
• Agitation
• Confusion
• Insomnia
• Hallucination
• Nightmares
• Impaired judgement
• Respiratory depression
• Pause in breathing (apnea)
• Headache
• Fatigue
• Pain at the injection site
• Excitement, confusion and depression in geriatric patients
• Paradoxical excitement and hyperactivity in pediatric patients
• Low blood pressure (hypotension)
• Slow heart rate (bradycardia)
• Fainting (syncope)

Less common side effects of phenobarbital include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Reduced urination (oliguria)
• Anemia caused by abnormally large red cells and vitamin B deficiency (megaloblastic folate-deficiency anemia)
• Low level of granulocyte immune cells (agranulocytosis)
• Low platelet count (thrombocytopenia)
• Mental dullness

Uncommon and rare side effects of phenobarbital include:

• Toxicity to the liver (hepatotoxicity)
• Low blood calcium levels (hypocalcemia)
• Hypersensitivity reactions including:
  • Skin rash
  • Swelling of tissue under the skin and mucous membranes (angioedema)
• Severe skin reactions including
  • Stevens-Johnson syndrome
  • Exfoliative dermatitis
• Softening of bones (osteomalacia)
• Rickets

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet: Schedule IV

• 15 mg
• 16 mg
• 30 mg
• 32 mg
• 60 mg
• 64.8 mg
• 65 mg
• 100 mg

Elixir: Schedule IV

• 20 mg/5mL

Injectable solution: Schedule IV

• 30 mg/mL
• 60 mg/mL
• 65 mg/mL
• 130 mg/mL

Adult:

Status Epilepticus

• Typically used after benzodiazepines and phenytoin fail to abort status epilepticus
• 15-18 mg/kg intravenous (IV) loading dose infused at 25-60 mg/min; prepare to support ventilation; may repeat in 20-minute intervals as needed; not to exceed 30 mg/kg

Seizures

• All types of seizure disorders, including partial, tonic-clonic, and myoclonic seizures
• 1-3 mg/kg/day oral/intravenous (IV) in 1-2 divided doses initially; adjust accordingly to maintain within the therapeutic serum concentration range

Sedation

• 30-120 mg/day orally divided two or three times daily; do not exceed 400 mg/day

Hypnotic

• 100-320 mg/day orally/intravenously/intramuscularly; do not administer for more than 2 weeks

Insomnia

• 100-200 mg orally at bedtime; do not exceed 400 mg/day

Dosing Considerations

• Antiepileptic therapeutic concentration range: 10-40 mcg/L (43-172 micromoles/L)
• Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation

Pediatric:

Status Epilepticus

• Infants and children: 15-20 mg/kg IV infused at a rate not to exceed 2 mg/kg/min; not to exceed 1000 mg/dose
• Children under 60 kg: IV rate at less than 30 mg/min
• May repeat with 5-10 mg/kg bolus dose after 15-30 min as needed; not to exceed the cumulative dose of 40 mg/kg

Seizures

• Neonates (less than 28 days): 3-5 mg/kg/day intravenously (IV)/orally in 1-2 divided doses
• Infants: 5-6 mg/kg/day intravenously (IV)/orally in 1-2 divided doses
• Children 1-5 years: 6-8 mg/kg/day intravenously (IV)/orally in 1-2 divided doses
• Children 6-12 years: 4-6 mg/kg/day intravenously (IV)/orally in 1-2 divided doses
• Children over 12 years: 1-3 mg/kg/day intravenously (IV)/orally in 1-2 divided doses, OR 50-100 mg two or three times daily

Sedation

• 2 mg/kg orally three times daily

Hypnotic

• 3-5 mg/kg orally at bedtime

Preoperative Sedation

• 1-3 mg/kg orally/intravenously/intramuscularly 1-1.5 hours before procedure

Hyperbilirubinemia (Off-label)

• Neonates: 5 mg/kg/day orally/intravenously (IV) once/day, OR divided every 12 hours for 3-6 days following birth
• Children under 12 years (chronic cholestasis): 1.5-4 mg/kg orally every 12 hours

Dosing Considerations

• Children under 6 years: Potential toxic dose 8 mg/kg
• Pediatric: Antiepileptic therapeutic concentration range: 15-30 mcg/L (43-129 micromoles/L)
• Long half-life permits once-daily dosing, if tolerated, for seizures; single daily dosing at bedtime recommended because of sedation

• Phenobarbital has a potential for addiction and may cause tolerance, and physical and psychological dependence, especially with prolonged use. Symptoms of phenobarbital dependence are similar to those of chronic alcoholism and discontinuation can cause severe withdrawal symptoms, including death. Treatment for phenobarbital dependence is careful and gradual withdrawal of the drug.
• Phenobarbital overdose can cause central nervous system (CNS) depression, pulmonary edema, circulatory collapse, cardiac arrest, and death. Treatment for phenobarbital overdose includes symptomatic and supportive care which may include ventilation. Stomach contents may be flushed out with induced vomiting or gastric lavage, in addition to the use of activated charcoal to absorb undigested drug in the gastrointestinal tract.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Phenobarbital has severe interactions with at least 33 different drugs.
• Phenobarbital has serious interactions with at least 165 different drugs.
• Phenobarbital has moderate interactions with at least 434 different drugs.
• Phenobarbital has mild interactions with at least 151 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information.

Check with your doctor or health care provider if you have any questions about the medication.

• Phenobarbital can cause fetal harm; use only for life-threatening emergencies during pregnancy.
• Use during the third trimester of pregnancy can cause withdrawal symptoms in the newborn, including hyperirritability and seizures, which may occur up to 2 weeks after birth.
• Use during labor does not affect uterine activity, however, it may cause respiratory depression in the newborn; resuscitation equipment must be available.
• Phenobarbital is excreted in breast milk; use with extreme caution.
• A registry is available for women exposed to phenobarbital during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry (888-233-2334 or http://www.aedpregnancyregistry.org).

• Phenobarbital can cause dependence; use with caution
• Take phenobarbital exactly as prescribed; do not take larger or more frequent doses
• Store phenobarbital safely out of reach of children
• In case of overdose, seek medical help immediately or contact Poison Control Center
• Phenobarbital can impair mental and physical abilities; do not engage in activities such as driving and operating heavy machinery
• Do not drink alcohol or take drugs that depress the central nervous system while on phenobarbital therapy